Table 2

Response to therapy: modified intent-to-treat population

ParametersInsulin glargine with or without metformin plus
Lixisenatide 20 µg once daily (n = 297)Insulin glulisine once daily (n = 298)Insulin glulisine thrice daily (n = 295)
FPG, mmol/L (mg/dL); n
 Baseline, mean ± SD6.6 ± 1.8 (119 ± 33); 2956.9 ± 2.0 (123 ± 36); 2956.7 ± 1.9 (120 ± 34); 294
 Week 26 LOCF, mean ± SD6.6 ± 2.0 (119 ± 35); 2956.7 ± 1.9 (120 ± 35); 2956.7 ± 2.0 (121 ± 36); 294
 LS mean change ± SE−0.2 ± 0.1 (–4 ± 3); 295−0.2 ± 0.1 (–4 ± 3); 295−0.1 ± 0.1 (–1 ± 3); 294
 LS mean (95% CI) treatment difference−0.0 (–0.32, 0.30)−0.2 (–0.48, 0.14)
(–0.2 [–5.7, 5.4])(–3.0 [–8.6, 2.6])
2-h PPG, mmol/L (mg/dL);* n/N
 Baseline, mean ± SD14.1 ± 3.6 (254 ± 65); 69/9013.8 ± 3.5 (249 ± 63); 55/8814.6 ± 3.5 (262 ± 63); 68/295
 Week 26 LOCF, mean ± SD10.2 ± 3.9 (184 ± 70); 69/9012.2 ± 3.4 (220 ± 60); 55/8812.7 ± 3.9 (229 ± 69); 68/295
 LS mean change ± SE−3.6 ± 0.6−1.6 ± 0.6−1.4 ± 0.6
(–66 ± 11); 69/90(–28 ± 11); 55/88(–25 ± 11); 68/295
 LS mean (95% CI) treatment difference−2.1 (–3.3, –0.8)−2.2 (–3.4, –1.1)
(–37.3 [–59.2, –15.3])(–40.2 [–61.1, –19.2])
HbA1c, % (mmol/mol); n
 Baseline after 12-week run-in optimization, mean ± SD7.8 ± 0.6 (62 ± 6.6); 2927.7 ± 0.6 (61 ± 6.6); 2927.8 ± 0.6 (62 ± 6.6); 295
 Week 26 LOCF, mean ± SD7.2 ± 0.8 (55 ± 8.7); 2927.2 ± 0.8 (55 ± 8.7); 2927.0 ± 0.7 (53 ± 7.7); 295
 LS mean change ± SE−0.6 ± 0.1 (–6.6 ± 1.1); 292−0.6 ± 0.1 (–6.6 ± 1.1); 292−0.8 ± 0.1 (–8.7 ± 1.1); 295
 LS mean (95% CI) treatment difference−0.1 (–0.17, 0.06)0.2 (0.10, 0.33)
(–0.5 [–1.9, 0.7])(2.3 [1.0, 3.5])
HbA1c <7% at week 26
 n/N (%)123/292 (42.1)112/292 (38.4)145/295 (49.2)
 Treatment difference, % (95% CI)3.7 (–4.03, 11.49)−7.3 (–15.07, 0.56)
HbA1c ≤6.5% at week 26
 n/N (%)60/292 (20.5)52/292 (17.8)91/295 (30.8)
 Treatment difference, % (95% CI)2.7 (–3.59, 9.01)−10.5 (–17.33, –3.59)
Body weight, kg; n
 Baseline, mean ± SD90.1 ± 17.4; 29588.4 ± 15.9; 29590.0 ± 17.2; 295
 Week 26 LOCF, mean ± SD89.4 ± 18.1; 29589.3 ± 16.3; 29591.3 ± 17.3; 295
 LS mean change ± SE−0.6 ± 0.3; 2951.0 ± 0.3; 2951.4 ± 0.3; 295
 LS mean (95% CI) treatment difference−1.7 (–2.26, –1.06)−2.0 (–2.59, –1.40)§
Patients with no weight gain; n/N (%)191/295 (64.7)108/295 (36.6)90/295 (30.5)
 Weighted average response rate
  (95% CI) treatment difference (%)28.1 (20.5, 35.8)34.2 (26.7, 41.7)
Insulin glargine dose, U/day; n
 Baseline, mean ± SD67 ± 32; 29265 ± 32; 29465 ± 27; 294
 Week 26 LOCF, mean ± SD67 ± 36; 29264 ± 36; 29461 ± 29; 294
 LS mean change ± SE from baseline to week 260.7 ± 1.0; 292−0.1 ± 1.0; 294−3.1 ± 1.0; 294
 LS mean (95% CI) treatment difference0.8 (–1.41, 2.92)3.8 (1.66, 6.00)
Daily insulin glulisine dose, units; n
 Week 26 LOCF, mean ± SD10 ± 8; 29520 ± 13; 293
Total daily insulin dose (glargine + glulisine), units; n
 Week 26 LOCF, mean ± SD67 ± 32; 29274 ± 39; 29581 ± 34; 294
Exploratory analyses
 Patients with ≥2% weight loss; n (%)97 (32.9)33 (11.2)32 (10.8)
  Weighted average response rate treatment difference, % (95% CI)21.7 (15.27, 28.11)22.0 (15.61, 28.43)
 Patients with ≥3% weight loss; n (%)69 (23.4)21 (7.1)18 (6.1)
  Weighted average response rate treatment difference, % (95% CI)16.3 (10.69, 21.97)17.3 (11.75, 22.85)
 Patients with ≥5% weight loss; n (%)36 (12.2)11 (3.7)7 (2.4)
  Weighted average response rate treatment difference, % (95% CI)8.5 (4.13, 12.86)9.8 (5.69, 13.98)
  • Summary statistics (mean ± SD) for HbA1c, FPG, 2-h PPG, and body weight were based on modified intent-to-treat population; all available data were included in the analysis. An ANCOVA model was used for calculation of LS mean treatment difference for HbA1c, FPG, 2-h PPG, and body weight, with treatment groups, week – 1 strata of HbA1c (<8 or ≥8% [<64 or ≥64 mmol/mol]), metformin use (yes or no) strata at randomization, and country as fixed effects, and the corresponding baseline value as a covariate. Patients with both baseline and week 26 (LOCF) measurements are included. LOCF, last observation carried forward.

  • *After a standardized meal in patients administered treatment before breakfast.

  • †Weighted average of proportion difference between treatment groups from each strata (week – 1 strata of HbA1c [<8.0 or ≥8.0%], randomization strata of metformin use) using Cochran–Mantel–Haenszel weights.

  • ‡Prespecified end point.

  • §P < 0.0001.